The A3 adenosine receptor, a Gi protein-associated cell surface receptor, was proposed as a target to combat cancer and inflammation. The receptor is highly expressed in various tumor cell types while expression in adjacent normal tissues is relatively low. Activation of the receptor by a specific synthetic agonist induces modulation of downstream signal transduction pathways which include the Wnt and the NF-kB, resulting in tumor growth inhibition (1-5).
In vivo studies have shown that A3AR agonists inhibit the development of colon, prostate and pancreatic carcinomas as well as melanoma and hepatoma. A3AR agonists were also been shown to act as anti-inflammatory agents by ameliorating the inflammatory process in different experimental autoimmune models such as rheumatoid arthritis, Crohn's disease and multiple sclerosis (6-10). It was proposed also that the A2A and A3 receptors mediate the anti-inflammatory effects of methotrexate (11).
A3 adenosine receptor (A3AR) expression levels are elevated in cancer cells as compared to normal cells (12). Thus, the A3AR expression level has been described as a means for the diagnosis of cancer (13). In addition, A3AR expression levels have also been described to be elevated in peripheral blood cells of patients with colorectal cancer (14).